Huan Yang

Background: Acute exacerbations of generalized myasthenia gravis (gMG) require rapidprompt rescue treatment, butbut comparative evidence regardingon the clinical effectiveness and economic burden of plasma exchange (PE), intravenous immunoglobulin (IVIG), and efgartigimod (EFG) remains limited. Methods: We conducted a retrospective multicenter study using clinical and economic data from 15 hospitals in China. Patients hospitalized for acute exacerbation of gMG between April 1, 2019, and April 1, 2025, were screened. Admissions involving PE, IVIG, or EFG alone were included in the primary three-group analysis, while sequential treatment regimens were evaluated separately in an exploratory sensitivity analysis. Treatment-group balance was addressed using multinomial propensity scores and generalized overlap weighting. The primary efficacy and economic outcomes were QMG improvement and total hospital cost, respectively, with Holm adjustment for multiple comparisons. Findings: Of 475 admissions screened, 374 admissions among 333 unique patients met the eligibility criteria, including 169 PE, 83 IVIG, 67 EFG, and 55 sequential-treatment admissions. The primary three-group analysis included 319 admissions. After overlap weighting, QMG improvement was greater with IVIG than with PE (adjusted mean difference 2.760 points, 95% CI 1.077–4.443; Holm-adjusted P=0.007), with EFG than with PE (5.197, 3.703–6.692; P<0.001), and with EFG than with IVIG (2.438, 0.621–4.254; P=0.019). Total hospital cost was higher with IVIG than with PE (ratio of adjusted means 1.599, 95% CI 1.193–2.143; Holm-adjusted P=0.007) and lower with EFG than with IVIG (0.595, 0.446–0.794; P=0.003), whereas EFG and PE did not differ significantly. As secondary findings, rescue-treatment costs and MG-related drug costs were higher with both IVIG and EFG than with PE, while the MG-ADL findings were sensitive to missing-data assumptions. However, after exclusion of the largest contributing center, none of the QMG or total-cost comparisons remained statistically significant. In subgroup analysis, no QMG or MG-ADL subgroup interaction was supported after Benjamini–Hochberg correction. Interactions were identified only for rescue-treatment cost by MGFA severity and pre-intervention clinical state. Conclusions: EFG was associated with greater short-term QMG improvement than PE, without evidence of higher total hospital costs. These findings support EFG as a potential rescue-treatment option, although the sensitivity of the estimates to center composition warrants prospective confirmation.

Aims: To compare the real‐world effectiveness, surgical and economic outcomes of preoperative rapid antibody clearance therapy (RACT: lymphoplasmapheresis (LPE), efgartigimod (EFG)) versus oral immunosuppressants (Oral IS) in generalized myasthenia gravis (gMG) patients undergoing thymectomy. Methods: This retrospective study included 78 patients (36 Oral IS, 42 RACT: 25 LPE, 17 EFG). Primary outcome: 3‐month postoperative quantitative myasthenia gravis (QMG) score. Secondary outcomes: 1‐month postoperative exacerbation rate, 3‐ and 6‐month MG activities of daily living (MG‐ADL), 6‐month QMG, surgical outcomes (operative time, blood loss, postoperative myasthenic crisis (POMC)), perioperative costs (pre‐ and post‐reimbursement). Propensity score overlap weighting balanced covariates. Sensitivity analyses used propensity matching; multiple imputation handled missing data. Results: After weighting, 3‐month QMG scores showed no significant difference between RACT and Oral IS groups (mean difference (MD) −0.23, 95% CI: −2.99 to 2.54, p = 0.831) nor between the EFG and LPE subgroups (MD 1.15, 95% CI: −3.97 to 6.26, p = 0.567); similar for MG‐ADL. All groups improved over time ( p < 0.001). For EFG vs. LPE, 1‐month exacerbation rate was 43.3% vs. 26.1% ( p = 0.412). No significant between‐group differences between EFG and LPE were found in 6‐month QMG/MG‐ADL scores and surgical outcomes. EFG had higher preoperative pre‐reimbursement costs (MD 14,500 CNY, p = 0.026), but no cost differences remained after insurance. Sensitivity analyses confirmed robustness of the primary findings. Conclusion: Preoperative RACT effectively reduced QMG in gMG patients, with no significant postoperative medium‐term effectiveness and safety differences between RACT and Oral IS. Similarly, no significant differences in postoperative medium‐term effectiveness, safety, or post‐reimbursement costs were observed between EFG and LPE.

Exhausted T cells (Tex), characterized by impaired cytotoxic function, play a detrimental role in anti-tumor and anti-infection immunity but represent promising therapeutic targets for autoimmune diseases. Persistent exposure to auto-antigens drives autoreactive CD8+ or CD4+T cells toward an exhausted-state, thereby mitigating excessive damage to healthy tissues. Inducing T cell exhaustion may offer a targeted approach to suppress pathological autoimmunity. In this review, we describe the markers, characteristics, and developmental phases of T cell exhaustion, discuss its close association with autoimmune diseases, and highlight Tex as a potential biomarker. We also summarize Tex-targeted therapeutic strategies, including inhibitory receptor activation, TCR overstimulation, and metabolic intervention, to provide insights for future treatments. The clinical translation gap of Tex-targeted therapy has also been proposed from stability, safety, and disease-specific considerations. Although challenges remain in areas such as antigen specificity and tenuous tolerance, therapies targeting Tex hold considerable potential to disrupt pathogenic circuits, realize disease remission, and reduce the risk of relapse in autoimmune diseases.

Tacrolimus (TAC) is recommended for the patients with drug tolerance or respond poorly to other conventional immunosuppressants in myasthenia gravis (MG), but its effectiveness is influenced by dose and genetic polymorphism. Studies suggest that HLA polymorphisms are significantly associated with susceptibility to MG, but the relationship between HLA and TAC efficacy in MG has not been explored. In this paper, we investigated the correlation between TAC therapeutic efficacy and HLA in different MG subgroups. HLA‐C*03 was associated with a better response to TAC in patients with early‐onset MG, generalized MG, and those with a high concentration of TAC. While HLA‐A*11:01 showed poor responsiveness to TAC in generalized MG. Furthermore, computational docking was used to demonstrate the binding situation of HLA‐A with the TAC binding protein FKBP1A. It showed that HLA‐A*11:01 had a higher binding strength with FKBP1A than HLA‐C*03 , indicating that the combination of different types of HLA and FKBP1A may be one of the reasons affecting its therapeutic efficacy. This study highlights the influence of HLA on the efficacy of TAC among different MG subgroups, providing clues for precise treatment of MG with TAC.

Myasthenia gravis (MG) is a T/B cell-driven autoimmune disease. The immunomodulatory mechanisms of the common immunosuppressant tacrolimus (TAC) on the immune repertoire are unclear. This study investigated TAC's immunomodulatory effects via high-throughput sequencing of peripheral blood mononuclear cells from four MG patients pre- and post-four months of TAC monotherapy, revealing dynamic T-cell receptor (TCR) and B-cell receptor (BCR) repertoire remodeling. The immune repertoire of MG patients was characterized by a skewed usage of TRBV gene families compared to healthy controls, indicating an underlying immune dysfunction. Longitudinal analysis post-TAC therapy revealed potential downregulation of IGHV1-69 and IGHV3-43 gene frequencies (p < 0.05, FDR > 0.1), alongside non-significant trends toward shorter CDR3 lengths and reduced clonal diversity in both IGH and TRB (p > 0.05). The BCR repertoire underwent greater dynamic remodeling, while the TCR repertoire remained relatively stable, as evidenced by the persistence of dominant clones and overlapping TRB clones. BCR diversity and V or J gene usage in TCR and BCR showed potential associations with clinical severity. These data reveal skewed antigen recognition profiles in MG pathogenesis, with TAC orchestrating multimodal immunomodulation through peripheral immune repertoire reshaping.

Background: Ofatumumab (OFA), a humanized anti-CD20 monoclonal antibody, shows potential in myasthenia gravis (MG) with antibody against acetylcholine receptor (AChR-Ab), but comparative efficacy across AChR and muscle-specific kinase (MuSK) subtypes remains uncharacterized. Objectives: To evaluate OFA’s clinical and immunological effects in AChR-MG versus MuSK-MG, identify predictors of minimal symptom expression (MSE), and explore the dynamics of B-cell repopulation. Design: A retrospective study in a single center. Methods: Twenty-one refractory MG patients (13 MuSK+, 8 AChR+) received individualized OFA induction (Regimen 1: two 20 mg doses ⩾2 weeks apart; Regimen 2: single 20 mg dose) and maintenance (20 mg upon CD19 + B counts ⩾5 cells/μL repopulation or clinical exacerbation). Outcomes included time-to-MSE, Quantitative Myasthenia Gravis Score (QMGS) dynamics, prednisone reduction, and serial immunophenotyping (B-cell activating factor (BAFF), a proliferation-inducing ligand (APRIL), soluble CD40L (sCD40L), microphage migration inhibitory factor (MIF), and immunoglobulin). Results: MuSK-MG achieved faster MSE (median time: 6 vs 15 months, log-rank p = 0.164, age-adjusted Cox p = 0.027), and a higher 3-month improvement (92.3% vs 50.0%; p = 0.047). Earlier achievement of MSE was associated with shorter disease duration ( p = 0.038) and concomitant corticosteroid therapy ( p = 0.030). Prednisone doses decreased significantly over 6 months ( p = 0.029) without difference between groups ( p = 0.109). MuSK-MG showed synchronized BAFF/APRIL declines while AChR-MG presents transient BAFF elevation and sustained APRIL. BAFF levels showed a significant positive correlation with QMGS in MuSK-MG, while IgM/IgG positively correlated with QMGS in both subtypes. Median B cell-repopulation time was 47.7 days. Conclusion: OFA demonstrates superior efficacy in MuSK-MG with distinct immunological modulation. AChR-MG requires combinatorial strategies targeting compensatory pathways.

Emerging epidemiological evidence shows myasthenia gravis (MG) is associated with age-related biological processes, but its mechanism of causality remains

Nagane Y, et al. J Clin Neurol. 2026 ;22:e42. https://doi.org/10.3988/jcn.2025.0290

Glycosylation, a critical post-translational modification of proteins, is particularly evident in immunoglobulins (Ig), also known as antibodies, and plays